Evaluation of an alternative in vitro test battery for detecting reproductive toxicants
Evaluation of an alternative in vitro test battery for detecting reproductive toxicants
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DOI：
10.1016/j.reprotox.2013.03.002
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发表时间：
2013-07-01
影响因子：
3.3
通讯作者：
van der Burg, B.
中科院分区：
文献类型：
--
作者：
Piersma, A. H.;Bosgra, S.;van der Burg, B.
考虑到涉及的机制的复杂性，在发育和生殖毒理学中应用替代方法是具有挑战性的。一组互补的测试系统可能会比单一的检测方法更好地预测发育和生殖毒性。我们在试剂盒中测试了12种具有不同毒性作用机制的化合物，包括24种CALUX转录激活试验、小鼠心脏胚胎干细胞试验、ReProGlo试验、斑马鱼胚胎毒性试验以及两种细胞色素P17和细胞色素P19活性测定。电池正确地检测到了11/12种被测试的化合物，其中一种出现了假阴性，这可能是因为电池中没有这种化合物的具体作用机制。毒代动力学模型显示，毒性浓度在体内生殖毒性数据预期的范围内。这项研究说明了包含互补生物过程和机制的组合检测的附加值，增加了电池相对于单独检测的预测价值。(C)2013 Elsevier Inc.保留所有权利。
The application of alternative methods in developmental and reproductive toxicology is challenging in view of the complexity of mechanisms involved. A battery of complementary test systems may provide a better prediction of developmental and reproductive toxicity than single assays. We tested twelve compounds with varying mechanisms of toxic action in an assay battery including 24 CALUX transcriptional activation assays, mouse cardiac embryonic stem cell test, ReProGlo assay, zebrafish embryotoxicity assay, and two CYP17 and two CYP19 activity assays. The battery correctly detected 11/12 compounds tested, with one false negative occurring, which could be explained by the absence of the specific mechanism of action of this compound in the battery. Toxicokinetic modeling revealed that toxic concentrations were in the range expected from in vivo reproductive toxicity data. This study illustrates added value of combining assays that contain complementary biological processes and mechanisms, increasing predictive value of the battery over individual assays. (c) 2013 Elsevier Inc. All rights reserved.